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Bayer was born and raised in Orange, Ohio,[2] the daughter of Carolyn (née Polster) and Todd Bayer.[3] She graduated from Orange High School in 2000[4] and attended the University of Pennsylvania where she majored in communications and French,[5] graduating in 2004. Her older brother Jonah is a music journalist and musician who has written for various music and guitar magazines, and has appeared as a music correspondent on Fuse TV, as well as being the guitarist for punk band United Nations.[6][7] Bayer had leukemia, fighting it throughout her childhood after being diagnosed with the disease at a young age.[3]

While attending college, Bayer interned on the television shows Sesame Street and Late Night with Conan O'Brien and participated in the cast of Bloomers, an all-female musical and sketch comedy troupe.[8] Bayer is of Ashkenazi Jewish ancestry and was part of the all-Jewish cast of Second City's stage show Jewsical: The Musical, a musical that presented a comedic take on Jewish life and culture.[9]

Bayer played the role of Kate Clark in the Chicago-based feature comedy Off the Cuff.

Bayer joined the cast of Saturday Night Live as a featured player on September 25, 2010. After Kristen Wiig's departure, beginning with the 2012–2013 season, Bayer was promoted to a repertory status. Some of her recurring sketches include a parody of Fox & Friends, which she does with Taran Killam and Bobby Moynihan, as well as The Miley Cyrus Show, which she did with Jason Sudeikis.